PROJECT ABSTRACT Glaucoma is a common neurodegenerative disease which is the 2nd leading cause of blindness in the United States. With the aging baby boomer population, these numbers will continue to increase exponentially over the next few decades. With glaucomatous progression, there is ultimately damage to the optic nerve which results in peripheral vision loss. It has been shown in many prior studies that lowering the intraocular pressure (IOP) is the best way to minimize the risk of progression of the disease. The majority of glaucoma patients are treated with topical drops. However, there are many inherent issues that prevent adequate therapy including corneal transport inadequacy, systemic side effects, cost, ocular surface irritation, compliance, and drop instillation. Because of these issues, patients essentially do not receive adequate therapy for their disease and are more likely to have disease progression associated with vision loss. Therefore, there is a significant need to create alternative techniques for drug delivery directly to the trabecular meshwork and Schlemm's canal. Retroject, Inc. is developing the disposable Retroject device to deliver various glaucoma drugs to these targeted sites. This proposal has two aims. In Aim 1, injections of an FDA-approved drug will be injected into the eyes of human glaucoma patients using the Retroject device. IOP and aqueous humor outflow facility will be evaluated to determine the effect of the injection on these parameters. In Aim 2, safety and injection comfort will be assessed. The degree of safety will be assessed through a variety of means including the validated Patient Comfort Assessment Guide, corneal endothelial counts, corneal pachymetry, and thorough anterior and posterior segment clinical exams. The confirmation of safety and efficacy of the Retroject device in human glaucoma patients would provide significant support for its potential in glaucoma patient therapy. Successful achievement of these specific aims will ultimately lead to an STTR Phase II Proposal to not only enlarge the size of the clinical trial but also to assess a variety of glaucoma drugs with the Retroject device. Nanoparticles of various drugs which can release drug over 2-3 months will be injected into Schlemm's canal. This would minimize the compliance issues associated with topical therapy and could significantly change the way we treat our glaucoma patients.